论文部分内容阅读
目的:研究尼曼匹克C1样1(Niemann Pick C1 like 1,NPC1L1)基因启动子-762T>C多态性的活性差异及药物对其的调节作用。方法:分别构建含NPC1L1基因-762T>C多态性的T/C等位基因启动子荧光酶报告基因,测定启动子活性以及不同药物处理后启动子活性的改变。结果:含T或C等位基因的NPC1L1基因启动子活性无统计学差异(P>0.05)。外源性胆固醇和依泽麦布均在高浓度抑制两种启动子活性,辛伐他汀则增强两种启动子活性(P<0.05),但两种基因型启动子之间对药物依泽麦布和辛伐他汀的反应无统计学差异(P>0.05)。结论:胆固醇和依泽麦布能抑制NPC1L1转录活性活性,辛伐他汀则增强NPC1L1转录活性,而-762T>C多态性不影响启动子活性及药物反应。
OBJECTIVE: To study the differences in the activities of promoter -762T> C polymorphisms in Niemann Pick C1-like 1 (NPC1L1) gene and the regulatory effect of the drugs. Methods: The luciferase reporter gene of T / C allele with NPC1L1 gene -762T> C polymorphism was constructed and the changes of promoter activity and promoter activity after different drugs were determined. Results: There was no significant difference in promoter activity of NPC1L1 gene with T or C allele (P> 0.05). Exogenous cholesterol and ezetimibe both inhibited the activity of the two promoters at high concentrations, while simvastatin increased both of the promoters (P <0.05), but the two genotype promoters showed no effect on drug ezekiel The reaction between cloth and simvastatin was not statistically different (P> 0.05). CONCLUSION: Cholesterol and ezetimibe inhibit NPC1L1 transcriptional activity while simvastatin enhances NPC1L1 transcriptional activity, whereas -762T> C polymorphism does not affect promoter activity and drug response.